Impact of Laparoscopic and Conventional Surgery on Kupffer Cells, Tumor-Associated CD44 Expression, and Intrahepatic Tumor Spread

Abstract

Background: The oncologic feasibility of laparoscopic surgery for the cure of colorectal cancer is under debate. The effect of laparoscopic colorectal cancer resection on hepatic tumor spread has not yet been clarified. Hypothesis: Laparoscopic surgery affects cellmediated immune response and hepatic tumor spread dependent on intraperitoneal insufflation. Methods: Thirty WAG/Rij rats were randomized into 3 operative groups: carbon dioxide (CO 2) laparoscopy (n=10), "gasless" laparoscopy (n = 10), and laparotomy (n=10). To induce liver metastases, 50 000 CC531 colon carcinoma cells were injected into the portal vein during either laparoscopy or laparotomy. Twenty-eight days after injection, specimens were explanted, sectioned, and examined immunohistochemically for CC531 tumor cells (monoclonal antibody CC52), CD44v5, v6 (monoclonal antibody OX49), and Kupffer cells (monoclonal antibody HIS36). For quantification, a morphometric analysis system was applied. Data were analyzed using the Kruskal-Wallis, Dunn, and Holm tests. Results: No statistically significant differences in hepatic tumor growth were found between CO 2 laparoscopy and laparotomy (P=.37). However, compared with CO 2 laparoscopy and laparotomy, a significant decrease in intrahepatic tumor growth was found after gasless laparoscopy (P = .02). Kupffer cells had significantly decreased after CO 2 laparoscopy and laparotomy compared with after gasless laparoscopy (PϽ.001 and P=.002, respectively). CD44v5, v6 expression was significantly increased after CO 2 laparoscopy and laparotomy compared with after gasless laparoscopy (P=.002 and P=.05, respectively). Conclusions: Hepatic resistance to tumor growth is best preserved by gasless laparoscopy as opposed to CO 2 laparoscopy or laparotomy. The amount of intra-abdominal pressure with circulatory changes rather than the used gas may explain this finding. On the other hand, conventional laparoscopy vs laparotomy did not preserve hepatic immune function.

Saline-filled laparoscopic surgery: A basic study on partial hepatectomy in a rabbit model

“…On the other hand, recent report suggests that prolonged pneumoperitoneum for about 6 hours does not hamper liver function or cause liver damage after extended laparoscopic procedures [28]. Furthermore, it is undeniable that CO 2 pneumoperitoneum induces pathophysiological hemodynamic, pulmonary, renal, splanchnic, and endocrine changes [29]. According to two papers published by Chiu AW, et al [30,31], peritoneal insufflation of CO 2 to a pressure of 15mmHg elicited transient elevations of the aortic pressure, carotid arterial blood flow, and superficial renal cortical blood flow in porcine model.…”

“…Ishida et al [14] demonstrated that an elevated insufflation pressure facilitates the location of intraportally injected tumor cells in the liver, and that the pulmonary location of the tumor cells may not depend on insufflation pressures. It has been reported that CO 2 gas or acidosis itself inhibits phagocytosis by macrophages in the abdominal cavity, and that the ability to phagocytose intraoperative free tumor cells may be suppressed [14,29].…”

Enhanced Tumour Growth and Impaired Cellular Antitumoural Defence in Hepatic Colorectal Carcinoma Metastasis in Rats after Laparoscopy Compared to Open Surgery

“…Previous applications of the CC531s model in experimental laparoscopy were performed by intrasplenic 7 or intraportal 8,9 injection of the tumour cells, leading to multiple hepatic metastases after haematogeneous spread. In contrast, CC531s cells were injected subcapsularly in a nonsurgical oncological study to induce well-localised and accessible liver metastases.…”

“…A couple of experimental studies have assessed the influence of laparoscopy on postoperative outcome of colorectal carcinoma using various models. The assessment of haematogeneous hepatic tumour spread in rats 7,8 and mice 9 and of renal or cutaneous tumour growth after subcapsular 10 or subcutaneous 11 injection of colorectal carcinoma cells have led to controversial for and against arguments for the laparoscopic technique. Importantly, hepatic macrophages have been described as playing a key oncological role in cellular antitumoural defence in respect of enhanced experimental tumour growth following selective depletion of phagocytotic cells.…”

“…12,13 The influence of laparoscopy on the number and function of macrophages is not yet clear, although a lack of phagocytotic activity during laparoscopy 14 has been described and semiquantitative measurements of hepatic macrophages in experimental colorectal hepatic metastases without significant difference between laparoscopy and laparotomy have been performed. 8 Therefore, this study aims to assess the impact of experimental laparoscopy on postoperative hepatic growth of colorectal adenocarcinoma metastases and numbers of peritumoural macrophages assessed by MRI volumetry and immunofluorescent microscopic morphometry in a small-animal model.…”